Cartilage injuries and osteoarthritis affect over fifty million people each year and as of yet, there is no "cure" for their condition. The long term objective of this proposal is to develop an in vitro system for generating articular cartilage using fibroblastic cells, which can then be used in future repairs of cartilage. The specific aims will address the need for engineered cartilage and also the source of cells for the construct. Initially, (SA1) fibroblastic cells will be tested for the ability to differentiate into chondrocytes in monolayer culture when placed under various culture conditions. Differentiation will be assessed by expression of chondrocyte genes. Secondly, (SA2) these cells will be cultured in a three dimensional construct to determine to what extent they can form functional cartilage. This aim will have direct bearing on the application of adult "non-stem cells" in tissue engineering. Finally, (SA3) the cells will be transfected with anti-inflammatory or inhibitors of matrix degredation prior to three dimensional culture to examine the possibility of including these self-defense mechanisms in cartilage to be transplanted into patients. This would allow for the development of engineered tissues that are more able to withstand the transfer into a damaged environment. [unreadable] [unreadable]